A 52-Week, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study to Evaluate the Safety and Tolerability of GSK573719/GW642444 and GSK573719 in Subjects With Chronic Obstructive Pulmonary Disease (COPD) (COPD nDPI)

• incidence of adverse events [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
  the occurrence of any adverse event during the 52 week treatment period
  
  

• incidence of COPD exacerbations [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
  the incidence of any worsening symptoms of COPD treated with systemic corticosteroids, antibiotics, and/or resulted in hospitalization
  
  
• time to first COPD exacerbation [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
  the time to the first occurrence of worsening symptoms of COPD treated with systemic corticosteroids, antibiotics, or hospitalization
  
  
• clinical laboratory tests [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
  any effects on hematology or clinical chemistry tests
  
  
• vital signs [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
  pulse rate and systolic and diastolic blood pressure
  
  
• 12 lead ECG assessments [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
  heart rate, QTc(f), overall interpretation
  
  
• Holter reading assessments [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
  24 hour cardiac monitoring-will measure important arrhythmias, overall interpretation
  
  
• Supplemental use of albuterol/salbutamol and/or ipratropium bromide [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
  will measure via subject entries on daily paper diary cards the number of puffs and/or nebules taken from albuterol/salbutamol and/or ipratropium bromide
  
  
• Percentage of rescue-free days [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
  Rescue free days refers to how many days albuterol/salbutamol and/or ipratropium bromide not used
  
  
• Trough forced expiratory volume in one second (FEV1) and forced vital capacity [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
  measures of lung function-FEV1-how much air is expelled from the lungs in one second after a full inspiration and FVC-the total amount of air expelled from the lungs after a full inspiration
  
  

Several studies have demonstrated the efficacy and safety of combining an individual LABA compound plus an individual LAMA compound in COPD. These studies have shown the combination of these two products to be superior to either agent alone on a variety of outcomes in COPD. The beneficial effects of this combination regimen are likely due to the different mechanisms of action of the two bronchodilators (smooth bronchial muscle relaxation from activation of beta2 receptors from the LABA product and inhibition of acetylcholine-mediated smooth bronchial muscle contraction via blockade of muscarinic receptors from the LAMA product). The availability of a LABA/LAMA combination in one product instead of two individual products is a technical and therapeutic advancement in the pharmacological armamentarium for COPD and may lead to increased patient compliance due to once-daily administration. The purpose of this 52-week study is to evaluate the long-term safety (in terms of adverse events, COPD exacerbations, laboratory, ECG, and Holter findings, vital signs, use of rescue medication, and lung function) of GSK573719/GW642444 Inhalation Powder 125/25mcg in subjects with COPD. The long-term safety of GSK573719 Inhalation Powder 125mcg will also be evaluated. A placebo arm is included to evaluate these products compared to an inactive control. All treatments will be delivered once-daily via the nDPI. This study will establish the long-term safety profile of GSK573719/GW642444 Inhalation Powder 125/25mcg once-daily in subjects with COPD. The safety profile of GSK573719 Inhalation Powder125mcg once-daily will also be evaluated.